Methods for detecting interaction between a test moiety and a plurality of target moieties

Abstract

This invention relates generally to the field of microarray technology. In particular, the invention provides an integrated microarray device, which device comprises a substrate comprising a plurality of distinct microlocations and a plurality of microarray chips, wherein the number of said microlocations equals to or is more than the number of said microarray chips. In preferred embodiments, the devices also comprises a temperature controller at some or all of the microlocations. The use of the integrated microarray devices for detecting interactions among various moieties in various fields, such as clinical diagnostics, drug discovery, environmental monitoring and forensic analysis, etc., are further provided.

1. A method for detecting interaction between a test moiety and a plurality of target moieties, which method comprises:
 a) providing an integrated microarray device, which device comprises a substrate comprising a plurality of distinct microlocations and a plurality of microarray chips, wherein the number of said microlocations equals to or is more than the number of said microarray chips, and a plurality of target moieties attached to said microarray chips, and wherein the microlocations are in a well format comprising a plurality of wells wherein all of the wells are defined by inside and outside walls connected by thin girders wherein the thin girders and inside and outside walls of the wells form a space to contain an inert gas and thermally insulate adjacent wells from each other; 
 b) contacting a test moiety with said plurality of target moieties provided in step a); and 
 c) detecting interaction between said test moiety and said plurality of target moieties. 
 
     
     
       2. The method of  claim 1 , wherein the integrated microarray device comprises a substrate comprising a plurality of distinct microlocations and each of the microlocations comprises a microarray chip and a temperature controller. 
     
     
       3. The method of  claim 1 , wherein the interaction being detected are interaction(s) among moieties selected from the group consisting of a cell, a cellular organelle, a virus, a molecule and an aggregate or complex thereof. 
     
     
       4. The method of  claim 1 , wherein the plurality of target moieties is a plurality of genes, gene fragments or their encoded products. 
     
     
       5. The method of  claim 4 , wherein the plurality of genes, gene fragments or their encoded products are involved in a biological pathway, belong to a group of proteins with identical or similar biological function, expressed in a stage of cell cycle, expressed in a cell type, expressed in a tissue type, expressed in an organ type, expressed in a developmental stage, proteins whose expression and/or activity is altered in a disease or disorder type or stage, or proteins whose expression and/or activity is altered by drug or other treatments. 
     
     
       6. The method of  claim 1 , wherein interaction between a plurality of target moieties and a plurality of target moieties are detected. 
     
     
       7. The method of  claim 1 , wherein interaction between a plurality of target moieties and a plurality of target moieties are detected simultaneously or sequentially. 
     
     
       8. The method of  claim 1 , wherein the substrate comprises silicon, plastic, glass, ceramic, rubber, polymer or a composite thereof. 
     
     
       9. The method of  claim 8 , wherein the silicon is silicon dioxide or silicon nitride. 
     
     
       10. The method of  claim 1 , wherein the substrate comprises a surface that is hydrophobic or hydrophilic. 
     
     
       11. The method of  claim 1 , wherein the substrate comprises a surface that is porous or nonporous. 
     
     
       12. The method of  claim 1 , wherein the microlocations and/or the microarray chips are fabricated on the substrate. 
     
     
       13. The method of  claim 1 , which comprises (12) n  number of microlocations, wherein n is an integer that is at least 1. 
     
     
       14. The method of  claim 1 , wherein the microlocations are evenly or unevenly distributed on the substrate. 
     
     
       15. The method of  claim 1 , wherein the number of microlocations and the distance among the microlocations correspond to a standard microtiter plate. 
     
     
       16. The method of  claim 1 , wherein the microlocations are in a thermally insulated flat surface format. 
     
     
       17. The method of  claim 16 , which comprises (12) n  number of wells, wherein n is an integer that is at least 1. 
     
     
       18. The method of  claim 16 , which comprises 96, 384 or 1,536 wells. 
     
     
       19. The method of  claim 16 , wherein the wells have a geometry selected from the group consisting of circle, oval, square, rectangle, triangle and other irregular shape(s). 
     
     
       20. The method of  claim 16 , wherein the wells have identical or different shapes. 
     
     
       21. The method of  claim 1 , wherein at least one of the microlocations is in fluid contact with a fluid source or fluid passage outside the device. 
     
     
       22. The method of  claim 1 , wherein all of the microlocations are in fluid contact with a fluid source or fluid passage outside the device. 
     
     
       23. The method of  claim 1 , wherein at least two of the microlocations are in fluid contact with each other. 
     
     
       24. The method of  claim 1 , wherein all of the microlocations are in fluid contact with each other. 
     
     
       25. The method of  claim 1 , wherein each of the microlocations comprises a microarray chip. 
     
     
       26. The method of  claim 1 , wherein the microarray chips have identical or different densities. 
     
     
       27. The method of  claim 1 , wherein the microarray chips have a density of (100) n  spots/cm 2 , wherein n is an integer that is at least 1. 
     
     
       28. The method of  claim 1 , wherein at least one of the microarray chips has a density that is less than or equals to 400 spots/cm 2 . 
     
     
       29. The method of  claim 1 , wherein all of the microarray chips have a density that is less than or equals to 400 spots/cm 2 . 
     
     
       30. The method of  claim 1 , wherein at least one of the microarray chips has attached thereto a plurality of moieties. 
     
     
       31. The method of  claim 30 , wherein the microarray chip(s) has attached thereto a plurality of moieties on facing up or down direction. 
     
     
       32. The method of  claim 30 , wherein each of the moieties is selected from the group consisting of a cell, a cellular organelle, a virus, a molecule and an aggregate or complex thereof. 
     
     
       33. The method of  claim 32 , wherein the cell is selected from the group consisting of an animal cell, a plant cell, a fungus cell, a bacterium cell, a recombinant cell and a cultured cell. 
     
     
       34. The method of  claim 32 , wherein the cellular organelle is selected from the group consisting of a nuclei, a mitochondrion, a chloroplast, a ribosome, an ER, a Golgi apparatus, a lysosome, a proteasome, a secretory vesicle, a vacuole and a microsome. 
     
     
       35. The method of  claim 32 , wherein the molecule is selected from the group consisting of an inorganic molecule, an organic molecule and a complex thereof. 
     
     
       36. The method of  claim 35 , wherein the inorganic molecule is an ion selected from the group consisting of a sodium, a potassium, a magnesium, a calcium, a chlorine, an iron, a copper, a zinc, a manganese, a cobalt, an iodine, a molybdenum, a vanadium, a nickel, a chromium, a fluorine, a silicon, a tin, a boron and an arsenic ion. 
     
     
       37. The method of  claim 35 , wherein the organic molecule is selected from the group consisting of an amino acid, a peptide, a protein, a nucleoside, a nucleotide, an oligonucleotide, a nucleic acid, a vitamin, a monosaccharide, an oligosaccharide, a carbohydrate, a lipid and a complex thereof. 
     
     
       38. The method of  claim 1 , wherein at least two of the microarray chips have attached thereto a plurality of moieties. 
     
     
       39. The method of  claim 38 , wherein each of the microarray chips has attached thereto same type or different type of moieties. 
     
     
       40. The method of  claim 1 , wherein each of the microarray chips has attached thereto a plurality of moieties. 
     
     
       41. The method of  claim 1 , wherein at least one of the microlocations comprises a temperature controller. 
     
     
       42. The method of  claim 41 , wherein each of the microlocations comprises a temperature controller. 
     
     
       43. The method of  claim 41 , wherein each of the temperature controller is individually controllable. 
     
     
       44. The method of  claim 41 , wherein the temperature controller is selected from the group consisting of a resistive heater, a bidirectional semiconductor temperature controller, a ceramic heater and an infrared heater. 
     
     
       45. The method of  claim 1 , wherein the substrate is an unitary unit. 
     
     
       46. The method of  claim 1 , wherein the substrate is an assembled unit, which can be disassembled into at least two parts.